Nuclear magnetic resonance spectroscopy instrumentation for probing intermolecular interactions Nuclear magnetic resonance spectroscopy in solution has evolved into a powerful technique for structure determination of proteins and nucleic acids. More recently, a number of NMR-based approaches have been developed to monitor and characterize intermolecular interactions. These approaches offer unique advantages over other techniques and find their utility in structural biology, chemical biology and even drug discovery. The use of differential labeling and the advent of TROSY-type techniques have provided an additional dimension to the use of NMR in the structural biology field in the identification and characterization of macromolecular interfaces. Moreover, NMR has also found an important role in the study and characterization of the interactions between small organic molecules and macromolecular targets, particularly useful in lead identification and optimization processes. We have recently successfully employed these techniques to characterize intermolecular interfaces and to subsequently guide the design of high affinity small molecule binders. At the interface between chemistry and biology, these applications of solution NMR spectroscopy allow early identification of key interaction sites between macromolecular complexes therefore providing rapid information on possible targeting sites in absence of atomic resolution X- ray structures of the complex. Expanding on our current unique capabilities and expertise in these areas of research, we request funds for a 700 MHz instrument equipped with accessories for a higher signal-to-noise ratio (cryoprobe) and laboratory automation (liquid handler and sample changer). The requested instrument will serve in part our San Diego Chemical Genomics Center, so that it would be available to the entire scientific community, and will also support three major multi- component projects in the areas of cell signaling pathways in cancer and host-pathogen interactions in infectious diseases. [unreadable] [unreadable] [unreadable]